Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of septicemia due to Capnocytophaga in pediatric bone marrow recipients are reported. These gram negative rods, which are part of the normal buccal flora, cause periodontitis and localized or systemic infections, usually in immunocompromised hosts. Severe, prolonged neutropenia and mucitis due to chemotherapy and/or radiotherapy are risk factors for this opportunistic infection. Recovery can be achieved with most of the drug combinations including a beta-lactam used in hematology.
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PMID:[Capnocytophaga septicemia during bone marrow transplantation. Apropos of 2 cases]. 229 93

Capnocytophaga ochracea is a gram-negative, fusiform bacillus which is part of the normal human oral flora. This organism is often isolated from periodontal lesions of patients with periodontitis and is associated with sepsis in granulocytopenic patients. We report here a case of endocarditis caused by C. ochracea.
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PMID:Endocarditis caused by Capnocytophaga ochracea. 338

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis. Absolute neutrophil counts ranged from 114 to 2580/mm3. Diminished and delayed migration of PMN into a skin "window" occurred in B. Random and directed PMN migration under agarose toward f-Met-Leu-Phe, pepstatin A, and zymosan-activated serum were severely diminished in both patients. At 10(-7) M f-Met-Leu-Phe, mean random and directed migration were 52 and 23% (A, n = 3) and 48 and 13% (B, n = 4) of controls. These results were independent of incubation time and chemoattractant concentration. Patients' PMN had diminished quantitative nitroblue tetrazolium reduction compared to controls. B had a significant defect in PMN bactericidal activity with Escherichia coli with less than 0.2 log killing at 2 h. These results further characterize the defect in PMN migration reported by Beaudet et al. (J Pediatr 97:906, 1980). The finding of other abnormalities of PMN function suggests a metabolic defect in the neutrophil which may be related to the microsomal membrane defect in hepatocytes in glycogen storage disease type IB.
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PMID:Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB. 345 31

A patient receiving immunosuppressive treatment for multiple myeloma became granulocytopenic, and acute glossitis developed. Blood cultures were positive for Capnocytophaga, a fastidious Gram-negative bacillus that is known to be part of the normal oral flora and a pathogen for periodontitis. The infection responded to treatment with antibiotics, including penicillin G, to which the organism was sensitive. This is one of the first reports of Capnocytophaga septicemia, and suggests that this organism may be an important pathogen in immunosuppressed patients with oral mucosal lesions.
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PMID:Septicemia caused by Capnocytophaga in a granulocytopenic patient with glossitis. 738 86

Fifteen Bacteroides forsythus strains freshly isolated from patients with periodontitis were used together with three collection strains and one type strain for characterization of growth on various media; determination of enzymatic profiles, antibiotic susceptibility profiles, 16S rRNA ribotypes, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) outer membrane protein profiles, and pathogenicity; and gas chromatography analysis by using a wound chamber model in rabbits. All strains were stimulated by N-acetylmuramic acid, while one strain needed a further supplement such as yeast extract for optimal growth. All strains showed trypsin-like activity. While 10 different ribotypes were found, the SDS-PAGE profiles revealed similar patterns for all strains. All strains were sensitive to penicillin G (MICs, <0.5 microg/ml), ampicillin (MICs, <1.0 microg/ml), amoxicillin (MICs, <0.38 microg/ml), metronidazole (MICs, <0.005 microg/ml), tetracycline (MICs, <0.19 microg/ml), doxycycline (MICs, 0.05 microg/ml), erythromycin (MICs, <0.4 microg/ml), and clindamycin (MICs, <0.016 microg/ml), while they were less sensitive to ciprofloxacin (MICs, <4 microg/ml). B. forsythus did not cause abscess formation by monoinoculation. B. forsythus coinoculated with Fusobacterium nucleatum ATCC 10953 caused abscess formation in 75% of rabbits, while it caused abscess formation in 100% of rabbits when it was coinoculated with Porphyromonas gingivalis FDC 381. In the case of the latter combination, four of six rabbits died of sepsis after 6 to 7 days, and P. gingivalis and B. forsythus were recovered from the heart blood at a proportion of 10:1. B. forsythus strains were highly virulent and invasive in combination with P. gingivalis.
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PMID:Characterization of Bacteroides forsythus isolates. 916 47

The effect of two arginine-specific cysteine proteinases (gingipain Rs) from Porphyromonas gingivalis, a causative bacterium of adult periodontitis, on human blood coagulation was investigated. Activated partial thromboplastin time and prothrombin time were shortened by these proteinases, with a 95-kDa gingipain R containing adhesin domains being 5-fold more efficient in comparison to a 50-kDa gingipain R containing the catalytic domain alone. The 50-kDa enzyme reduced each coagulation time in several plasmas deficient in various coagulation factors, while it was ineffective in factor X-deficient plasma unless reconstituted with this protein. Each proteinase activated factor X in a dose- and time-dependent manner, with Michaelis constants (Km) being found to be lower than the normal plasma factor X concentration, strongly suggesting that factor X activation by gingipain Rs, especially the 95-kDa form which is strongly activated by phospholipids, could occur in plasma. This is the first report of factor X activation by bacterial proteinases and indicates that the gingipain Rs could be responsible for the production of thrombin and, indirectly, with the generation of prostaglandins, interleukin-1, etc., which have been found to be associated with the development of periodontitis induced by P. gingivalis infections. Furthermore, the data support the hypothesis that induction of blood coagulation by bacterial proteinases may be a causative agent in the pathogenesis of disseminated intravascular coagulation in sepsis.
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PMID:Activation of blood coagulation factor X by arginine-specific cysteine proteinases (gingipain-Rs) from Porphyromonas gingivalis. 918 12

Gram-positive anaerobic cocci (GPAC) are a heterogeneous group of organisms defined by their morphological appearance and their inability to grow in the presence of oxygen; most clinical isolates are identified to species in the genus Peptostreptococcus. GPAC are part of the normal flora of all mucocutaneous surfaces and are often isolated from infections such as deep organ abscesses, obstetric and gynecological sepsis, and intraoral infections. They have been little studied for several reasons, which include an inadequate classification, difficulties with laboratory identification, and the mixed nature of the infections from which they are usually isolated. Nucleic acid studies indicate that the classification is in need of radical revision at the genus level. Several species of Peptostreptococcus have recently been described, but others still await formal recognition. Identification has been based on carbohydrate fermentation tests, but most GPAC are asaccharolytic and use the products of protein degradation for their metabolism; the introduction of commercially available preformed enzyme kits affords a physiologically more appropriate method of identification, which is simple and relatively rapid and can be used in routine diagnostic laboratories. Recent reports have documented the isolation in pure culture of several species, notably Peptostreptococcus magnus, from serious infections. Studies of P. magnus have elucidated several virulence factors which correlate with the site of infection, and reveal some similarities to Staphylococcus aureus. P. micros is a strongly proteolytic species; it is increasingly recognized as an important pathogen in intraoral infections, particularly periodontitis, and mixed anaerobic deep-organ abscesses. Comparison of antibiotic susceptibility patterns reveals major differences between species. Penicillins are the antibiotics of choice, although some strains of P. anaerobius show broad-spectrum beta-lactam resistance.
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PMID:Gram-positive anaerobic cocci. 945 30

In order to determine the effect of bacterial proteinases on activation of the protein C system, a negative regulator of blood coagulation, two arginine-specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, a causative bacterium of adult periodontitis, were examined. Each enzyme activated human protein C in a dose- and incubation time-dependent manner. Interestingly, the form of enzyme being composed of a non-covalent complex containing both catalytic and adhesion domains (RgpA) produced activated protein C 14-fold more efficiently than RgpB which contained the catalytic domain alone. The kcat/Km value of RgpA was 18-fold higher than that of RgpB and comparable to that of the thrombin-thrombomodulin complex, the physiological activator of protein C. RgpA catalyzed protein C activation was augmented 1.4-fold by phospholipids, ubiquitous cell membrane components. Furthermore, RgpA, but not RgpB, could activate protein C in plasma and this resulted in a decrease of the protein C concentration in plasma, which is often observed in patients with sepsis during the development of disseminated intravascular coagulation (DIC). These data indicate that RgpA is a more potent activator of protein C than RgpB and suggest that only the former enzyme can cause protein C activation in vivo. The present study further suggests that bacterial proteinases may possibly contribute to the consumption of plasma protein C which predisposes to DIC and/or promotes a thrombotic tendency towards DIC in sepsis.
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PMID:Activation of protein C by arginine-specific cysteine proteinases (gingipains-R) from Porphyromonas gingivalis. 1006 39

There is an increasing amount of evidence suggesting a systemic link between periodontal disease in the pregnant mother and pre-term low birth weight (PLBW). Severe periodontitis affects at least 10% of the general population. The aetiology of periodontitis is essentially a bacterially induced inflammatory reaction within the attachment surrounding the teeth. Maternal infection has been linked with pre-term delivery. Normal pregnancy itself is associated with inflammatory changes very similar to those found in sepsis. Because the infected periodontal tissues can act as a reservoir for both bacterial products and inflammatory cytokines, it may be possible that periodontal infection and the resultant inflammation could be linked with PLBW. Current understanding suggests that prostaglandins and proinflammatory cytokines play a pivotal role in the initiation process because of the close relationship of inflammation and infection. High levels of maternally or fetally derived cytokines such as tumour necrosis factor alpha (TNFalpha) may enhance amniochorionic and decidual interleukin six (IL-6) expression. Prostaglandin E2 (PGE2) has also been associated with periodontitis and PLBW. Periodontitis is a possible risk factor for PLBW with an odds ratio of 2.30. For the majority of individuals affected with periodontitis, the condition is symptom-free until the disease is more advanced. Therefore there is the need for medical carers of pregnant patients to increase the awareness among pregnant women themselves. Although there is plenty of evidence associating periodontitis with PLBW, interventional studies for the treatment of periodontitis measuring the impact on PLBW are few in number. Therefore more good quality clinical trials are required to address this issue.
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PMID:Periodontitis and pregnancy. 1647 12

Lipid A structural modifications can substantially impact the host's inflammatory response to bacterial LPS. Bacteroides fragilis, an opportunistic pathogen associated with life-threatening sepsis and intra-abdominal abscess formation, and Bacteroides thetaiotaomicron, a symbiont pivotal for proper host intestinal tissue development, both produce an immunostimulatory LPS comprised of penta-acylated lipid A. Under defined conditions, Porphyromonas gingivalis, an oral pathogen associated with periodontitis, also produces an LPS bearing a penta-acylated lipid A. However, this LPS preparation is 100-1000 times less potent than Bacteroides LPS in stimulating endothelial cells. We analyzed Bacteroides and P. gingivalis lipid A structures using MALDI-TOF MS and gas chromatography to determine the structural basis for this phenomenon. Even though both Bacteroides and P. gingivalis lipid A molecules are penta-acylated and mono-phosphorylated, subtle differences in mass and fatty acid content could account for the observed difference in LPS potency. This fatty acid heterogeneity is also responsible for the peak "clusters" observed in the mass spectra and obfuscates the correlation between LPS structure and immunostimulatory ability. Further, we show the difference in potency between Bacteroides and P. gingivalis LPS is TLR4-dependent. Altogether, the data suggest subtle changes in lipid A structure may profoundly impact the host's innate immune response.
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PMID:The structurally similar, penta-acylated lipopolysaccharides of Porphyromonas gingivalis and Bacteroides elicit strikingly different innate immune responses. 1946 Apr 28


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